[39] In addition to IL-4 production, we found that production of IL-10 is a striking feature of adipose iNKT cell activation, not

typically observed for iNKT cells in liver or spleen.[3] Together, these studies show that iNKT cells are Th2 polarized compared with iNKT elsewhere, and may have regulatory potential based on their IL-10 production. It is now clear that inflammation plays an important role in obesity and the metabolic syndrome.[47] The resident immune system in adipose tissue is key to this process. The pathological expansion of adipose tissue in obesity is associated with major changes in the adipose immune system, resulting in inflammation, which contributes Alectinib concentration to local and whole body insulin resistance and type 2 diabetes. Recently, many immunometabolic studies have shed light on key players involved in the transformation from a homeostatic anti-inflammatory environment to a pathogenic pro-inflammatory one in obese adipose tissue. All resident immune cells identified so far have been shown to play some role in either the development

or protection from chronic inflammation that drives obesity-induced metabolic disorder.[3, 7, 48-57] This suggests that the adipose immune system is tightly controlled and highly interactive, with any aberrations effecting metabolism, either directly or through the interactions with other immune cells. Recently we, and others, added iNKT cells to the list of key players involved in obesity. In 2009, we reported that iNKT cells were depleted in adipose tissue of obese individuals compared selleck inhibitor with age-matched lean controls.[2] This defect has also been confirmed by other laboratories[7, 39] and suggests that iNKT cells may play a role in human obesity. There is also a defect in iNKT cells in murine adipose tissue and liver in diet-induced and genetic models of obesity.[3] Our study,[3] and others[39, 57, 58] have highlighted that adipose tissue iNKT cells protect against diet-induced obesity

and glucose intolerance through regulatory cytokine production (Fig. 1). First, it was noted that iNKT-deficient Montelukast Sodium mice on normal diets were heavier than their wild-type counterparts and displayed an increased tendency towards insulin resistance. This association of iNKT cell deficiency and insulin resistance was a trend that was not significant in mice fed a normal chow diet in our study and in a similar study from Qi and colleagues.[3, 57] However, Boes and colleagues found that this trend was significant, with both CD1d−/− and Ja18−/− mice displaying impaired glucose tolerance and insulin resistance with age on a standard low-fat diet.[7] Second, we, and many groups, noted that iNKT cell numbers in adipose tissue fell in mice fed a high-fat diet (HFD), similar to reduction in iNKT cell number in human obesity.